title: Role of the Transforming-Growth-Factor-β1 Gene in Late-Onset Alzheimer's Disease: Implications for the Treatment.
abstract: Late-onset Alzheimer's disease (LOAD) is the most common form of dementia in the elderly. LOAD has a complex and largely unknown etiology with strong genetic determinants. Genetics of LOAD is known to involve several genetic risk factors among which the Apolipoprotein E (APOE) gene seems to be the major recognized genetic determinant. Recent efforts have been made to identify other genetic factors involved in the pathophysiology of LOAD such as genes associated with a deficit of neurotrophic factors in the AD brain. Genetic variations of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), and transforming-growth-factor-β1 (TGF-β1) are known to increase the risk to develop LOAD and have also been related to depression susceptibility in LOAD. Transforming-Growth-Factor-β1 (TGF-β1) is a neurotrophic factor that exerts neuroprotective effects against ß-amyloid-induced neurodegeneration. Recent evidence suggests that a specific impairment in the signaling of TGF-β is an early event in the pathogenesis of AD. TGF-β1 protein levels are predominantly under genetic control, and the TGF-β1 gene, located on chromosome 19q13.1-3, con-tains several single nucleotide polymorphisms (SNPs) upstream and in the transcript region, such as the SNP at codon +10 (T/C) and +25 (G/C), which is known to influence the level of expression of TGF-β1. In the present review, we summarize the current literature on genetic risk factors for LOAD, focusing on the role of the TGF-β1 gene, finally discussing the possible implications of these genetic studies for the selection of patients eligible for neuroprotective strategies in AD.
authors.affiliation: IRCCS Associazione Oasi Maria S.S. - Institute for Research on Mental Retardation and Brain Aging, 94018 Troina, Enna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bosco
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferri
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Salluzzo
authors.forename: Sabrina
authors.initials: S
authors.lastname: Castellano
authors.forename: Maria
authors.initials: M
authors.lastname: Signorelli
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Santo Di
authors.initials: SD
authors.lastname: Nuovo
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.forename: Filippo
authors.initials: F
authors.lastname: Caraci
keywords: Alzheimer’s disease; Depression; Drugs; Genetic polymorphism; Risk factor; Transforming-growth-factor-β1.